The objective of this project is to determine biochemical risk factors for developments of lung cancer associated with cigarette smoking. This project will focus on xenobiotic metabolizing enzyme induction as a result of cigarette smoking in the baboon. The following processes will be evaluated: (1) enzyme induction, (2) enzyme metabolism, and (3) mutagen formation. The approach will be to utilize existing baboons with a documented smoking history, plus appropriate shams, to monitor the parameters outlined above. In phase I, existing smokers and shams will be compared. In phase II, a new group of smokers (previous shams) will be utilized to determine the effects of acquisition of cigarette smoking on the parameters listed above. In phase III, an 8-month period of smoking cessation will be studied, followed by a 7-month period of reacquisition of smoking (phase IV). These data will be analyzed to determine differences between chronic smokers vs. beginners and shams vs. controls and to determine the effects of smoking cessation, as well as reacquisition, in new and experienced smokers. These studies will form the basis for design of future studies to determine possible means of intervention or chemoprevention with the overall goal of decreasing the risk of lung cancer development.